基于网络药理学及分子对接探讨连花清咳片治疗新型冠状病毒肺炎的作用机制

Mechanism of Lianhua Qingke tablets in treatment of COVID-19 based on network pharmacology and molecular docking

目的基于网络药理学及分子对接预测连花清咳片治疗新型冠状病毒肺炎(coronavirus disease 2019,COVID-19)可能作用的靶点及信号通路。方法通过TCMSP,UniProt Knowledgebase及SwissTargetPrediction数据库获取连花清咳片的活性成分及相关靶点;通过GeneCards和OMIM获取COVID-19相关靶点;使用Cytoscape 3.9.0软件构建“连花清咳片-COVID-19”靶点调控网络,结合STRING数据库绘制蛋白相互作用网络(Protein-protein interaction networks,PPI);使用Metascape数据库对交集基因进行GO功能和KEGG通路富集分析。通过AutoDockTools1.5.6软件将关键作用靶点与主要活性成分进行分子对接验证。结果以口服生物利用度(oral bioavailability,OB)和类药性(drug-like properties,DL)作为筛选条件,获得连花清咳片中药物活性成分287个,药物疾病交集基因86个,核心靶点58个。KEGG富集分析预测连花清咳片治疗COVID-19主要涉及p53信号通路(p53 signaling pathway)、补体途径(complement and coagulation cascades)、细胞因子-细胞因子受体相互作用(cytokine-cytokine receptor interaction)等信号通路等。分子对接结果证实连花清咳片中主要活性成分与核心靶点具有较为稳定的结合活性。结论连花清咳片可能通过多成分、多靶点及多通路参与COVID-19的治疗。

Aim To predict the possible targets and signal pathways of Lianhua Qingke tablets in the treatment of novel coronavirus disease 2019(COVID-19)based on network pharmacology and molecular docking.Methods Through TCMSP,UniProt and swisstargetpredition databases,the active components and related targets of the pharmacological action of Lianhua Qingke tablets were obtained;COVID-19 related targets were obtained through GeneCards and OMIM databases;the target regulatory network of“Lianhua Qingke tablets-COVID-19”was constructed by using cytoscape3.9.0 software database,and the protein-protein interaction networks(PPI)were drawn by combining with STRING database;metascape database was used to annotate the GO function and analyze the pathway enrichment of KEGG.The key targets and main active ingredients were selected and verified by autoDockTools 1.5.6 software.Results Taking oral bioavailability(OB)and drug like properties(DL)as screening conditions,287 active ingredients in Lianhua Qingke tablets were obtained;there are 86 drug-disease intersection genes and 58 core targets.KEGG enrichment analysis predicted that Lianhua Qingke tablets mainly involved P53 signal pathway,complement and coagulation cascades,cytokine-cytokine receptor interaction and other signal pathways.The results of molecular docking showed that the main active components in Lianhua Qingke tablets had stable binding activity with core targets.Conclusion Lianhua Qingke tablets may participate in the treatment of COVID-19 through multi-component,multi-target and multi-pathway.